Autophagy in the human placenta throughout gestation.

Autophagy in the human placenta throughout gestation.
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DOI:
10.1371/journal.pone.0083475
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Yeh YL
Yeh YL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hung TH;Hsieh TT;Chen SF;Li MJ;Yeh YL

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据报道,自噬对于着床前发育和胚胎存活至关重要。然而,其在胎盘发育和妊娠期间自噬的调节中的作用仍不清楚。本研究的目的是:(1)通过描述整个妊娠期间人类胎盘中beclin-1、DRAM和LC 3B水平的变化来研究自噬;(2)确定自噬是否参与JEG-3细胞滋养层侵袭的调节(3)观察缺氧和缺糖对自噬的影响;(4)观察缺氧缺糖(OGD)后复氧和补充葡萄糖对正常足月妊娠原代细胞滋养层细胞自噬变化的影响。对代表不同妊娠阶段的40个胎盘样品的分析显示:(1)在妊娠早期和中期以及妊娠晚期阴道分娩的胎盘中,beclin-1、DRAM和LC 3B-II水平没有显著差异;(2)妊娠晚期剖宫产的胎盘与妊娠早期和中期以及妊娠晚期阴道分娩的胎盘相比,LC 3B-II水平较低; DRAM水平也低于妊娠早期和中期的胎盘;和(3)使用外植体培养物,在生理氧浓度下,妊娠早期和晚期的绒毛组织具有相似的自噬通量速率。敲除BECN 1、DRAM和LC 3B对JEG-3细胞的存活率和侵袭活性没有影响。另一方面,OGD引起的LC 3B-II在原代细胞滋养层细胞的水平显着增加,而氧气和葡萄糖的补充减少了这些变化。此外,beclin-1、DRAM和LC 3B-II的水平响应于氧和葡萄糖水平的变化而发生差异变化。 我们的研究结果表明,自噬参与人类胎盘的发展,氧和葡萄糖水平的变化参与细胞滋养层细胞自噬变化的调节。
Autophagy has been reported to be essential for pre-implantation development and embryo survival. However, its role in placental development and regulation of autophagy during pregnancy remain unclear. The aims of this study were to (1) study autophagy by characterizing changes in levels of beclin-1, DRAM, and LC3B in human placenta throughout gestation; (2) determine whether autophagy is involved in regulation of trophoblast invasion in JEG-3 cells (a choriocarcinoma cell line); (3) examine the effects of reduced oxygen and glucose on the autophagic changes; and (4) investigate the effect of reoxygenation and supplementation of glucose after oxygen-glucose deprivation (OGD) on the autophagic changes in primary cytotrophoblasts obtained from normal term pregnancy. An analysis of 40 placental samples representing different gestational stages showed (1) no significant differences in beclin-1, DRAM, and LC3B-II levels in placentas between early and mid-gestation, and late gestation with vaginal delivery; (2) placentas from late gestation with cesarean section had lower levels of LC3B-II compared to early and mid-gestation, and late gestation with vaginal delivery; levels of DRAM were also lower compared to placentas from early and mid-gestation; and (3) using explant cultures, villous tissues from early and late gestation had similar rates of autophagic flux under physiological oxygen concentrations. Knockdown of BECN1, DRAM, and LC3B had no effects on viability and invasion activity of JEG-3 cells. On the other hand, OGD caused a significant increase in the levels of LC3B-II in primary cytotrophoblasts, while re-supplementation of oxygen and glucose reduced these changes. Furthermore, there were differential changes in levels of beclin-1, DRAM, and LC3B-II in response to changes in oxygen and glucose levels. Our results indicate that autophagy is involved in development of the human placenta and that changes in oxygen and glucose levels participate in regulation of autophagic changes in cytotrophoblast cells.
DOI: 10.4161/auto.3438
发表时间: 2007-01-01
期刊: AUTOPHAGY
影响因子: 13.3
作者:
Crighton, Diane;Wilkinson, Simon;Ryan, Kevin M.
通讯作者: Ryan, Kevin M.
DOI: 10.1177/1933719107310709
发表时间: 2008-02-01
影响因子: 2.9
作者:
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通讯作者: Hsieh, T'sang-T'ang
DOI: 10.1016/j.placenta.2008.09.001
发表时间: 2008-11-01
期刊: PLACENTA
影响因子: 3.8
作者:
Shen, Z. -Y.;Li, E. -M.;Xu, L. -Y.
通讯作者: Xu, L. -Y.
DOI: 10.3109/14767058.2012.733764
发表时间: 2013-03-01
影响因子: 1.8
作者:
Curtis, Sophie;Jones, Carolyn J. P.;Heazell, Alexander E. P.
通讯作者: Heazell, Alexander E. P.
DOI: 10.1371/journal.pone.0040957
发表时间: 2012
期刊: PloS one
影响因子: 3.7
作者:
Hung TH;Chen SF;Lo LM;Li MJ;Yeh YL;Hsieh TT
通讯作者: Hsieh TT